Group of Cancer Cells Illustration (© fotoyou - stock.adobe.com)
HERSHEY, Pa. — In a breakthrough that could revolutionize cancer treatment, researchers at Penn State have developed a way to modify immune cells that can be activated by blue light — the same rays that come from your phones and computers — to infiltrate and destroy tumors.
This innovative approach could overcome one of the biggest challenges in cancer immunotherapy: treating solid tumors, which make up 90% of adult cancers and 40% of childhood cancers. The research, published in the Proceedings of the National Academy of Sciences, represents a radical departure from existing immunotherapy treatments.
“This technology is totally out of the box,” says senior author Nikolay Dokholyan, the G. Thomas Passananti Professor at the Penn State College of Medicine, in a media release. “It’s akin to CAR T-cell therapy, but here, the guiding principle is the ability of cells to infiltrate the tumor. I don’t know of another approach that is anything close to this.”
While treatments like CAR T-cell therapy have shown remarkable success in blood cancers, they’ve struggled to kill off solid tumors. These tumors are like fortresses, surrounded by dense barriers of proteins and cells that prevent immune cells from getting inside. Think of it as trying to squeeze through a brick wall – conventional immune cells simply can’t breach these defenses.
The Penn State team’s solution is ingenious. They modified immune cells called natural killer cells by engineering them with a light-sensitive protein that controls their shape and structure. When exposed to blue light, these modified cells undergo a remarkable transformation – they become more elongated and develop finger-like projections that help them move and interact with their environment.
“Even though natural killer cells are small, around 10 micrometers, upon activation of this protein with blue light, the immune cells changed shape and can squeeze into tiny holes around three micrometers in size. That’s enough to infiltrate tumor spheroids and kill them from the inside,” Dokholyan explains.
To put this in perspective, these cells are squeezing through spaces about 30 times smaller than the width of a human hair.
The researchers tested their modified cells against laboratory-grown tumors (called spheroids) created from human breast cancer, human cervical cancer, and mouse melanoma cells. Within seven days, the light-activated immune cells had successfully penetrated and killed the tumor cells. In contrast, unmodified natural killer cells could only attack the tumor’s surface and eventually gave up, allowing the tumor to continue growing.
While these results are promising, it’s important to note that this research is still in its early stages. The tests were conducted on laboratory-grown tumors, and more research will be necessary before this approach can be considered for use in patients. However, the potential implications are significant – if successful, this could offer a new way to treat the vast majority of cancers that current immunotherapies struggle to address.
The technology has already caught the attention of the scientific community, with the researchers filing a provisional patent application. The team is also exploring other ways to activate these modified immune cells, potentially opening up even more treatment possibilities.
Paper Summary
Methodology
In this study, researchers used a technique called optogenetics, which allows them to control cells with light. They focused on a protein called septin-7, which helps cells move through tight spaces, like the barriers found around tumors. By attaching a light-sensitive part to this protein, they created a version of septin-7 that could be turned on and off with blue light.
When exposed to blue light, the modified septin-7 caused immune cells to change shape, making them more efficient at squeezing through barriers and infiltrating tumors. The researchers tested this by modifying immune cells, such as natural killer cells and T-cells, and seeing how well they could move through artificial tumor models.
Key Results
The study found that when immune cells were modified with the light-sensitive septin-7 and exposed to blue light, they became better at moving through the tough barriers around tumors. These modified immune cells had more success getting inside tumor models in the lab compared to regular immune cells.
Once inside the tumors, the modified cells also showed a greater ability to kill cancer cells. The researchers saw the most significant results when they used blue light to activate the cells for specific periods, which helped them move through the barriers and fight the cancer more effectively.
Study Limitations
This study was conducted in a controlled lab setting using tumor models, which are not perfect replicas of real tumors in the human body. The researchers used blue light to activate the modified immune cells, but blue light doesn’t penetrate deeply into human tissues, which means it may be challenging to use this technique for tumors located deep within the body.
Additionally, the long-term effects of modifying septin-7 in immune cells are not yet fully understood, and further testing in animals and humans will be needed to confirm if this method can work in real cancer treatments.
Discussion & Takeaways
The researchers believe that this new method of modifying immune cells with a light-sensitive version of septin-7 could significantly improve the effectiveness of immunotherapy for solid tumors. Since solid tumors are harder for immune cells to penetrate than blood cancers, this approach could be a way to overcome those barriers.
This method could potentially be combined with other cancer treatments to create a more powerful, multi-pronged approach to fighting cancer. However, more research is needed to see if it will work as well in real patients as it did in the lab.
Funding & Disclosures
This research was supported by funding from the National Institutes of Health and the Passan Foundation. One of the authors has applied for a patent on the engineered septin-7 protein used in the study. No other competing financial interests were disclosed by the researchers.
